1. Field of the Invention
The invention broadly relates to a device and a method for its use in assisting thrombolysis in coronary arteries, cerebral arteries, peripheral arteries, and other vascular channels. In particular, the invention relates to a piezoelectric element shaped and mounted on the tip of a wire or a catheter for the delivery of directed ultrasonic energy useful in assisting thrombolysis, endovascular sonophoresis, vascular tumor lysis, vasospasm and other medical conditions where a source of intraluminal directed ultrasound is needed.
2. Description of Related Art
Thrombolysis using pharmacologic agents and mechanical agents such as balloon angioplasty are currently the primary forms of therapy for vascular occlusions caused by thombi or thromboemboli. Their major applications are in the coronary arteries, peripheral arteries, and other vascular channels where presence of a clot (thrombus) or other occlusional deposits such as plaque result in the restriction and the blockage of blood flow. Such restriction and blockage result in oxygen deprivation of the tissue supported by the blood supply. Oxygen deprivation and its effect s are known as "ischemia". If the blood supply is completely blocked so that ischemia continues for a prolonged period of time, the affected tissue suffers permanent damage. This is what occurs in myocardial infarction and stroke. If tissue damage is extensive enough, death may ensue.
There are two general methods of administering pharmacologic agents in thrombolysis. One involves systemic infusion and the other involves local intravascular infusion. The latter requires the placement near the occlusion of a catheter through which the thrombolytic agents are delivered. Both methods are based on the principal that pharmacologic agents such as urokinase, streptokinase and recombinant tissue plasminogen activator (rt-PA) will enzymatically lyse and dissolve the occluding thrombus or thromboembolus. They can be effective, especially against newly formed thrombus. However, the administration of these drugs can cause severe bleeding complications such as cerebral hemorrhage which may result in death. Further, the effective use of these agents frequently requires prolonged treatment times (measured in hours) during which the affected tissue continues to experience ischemia.
Balloon angioplasty operates by inserting a deflated balloon through the occluded segment of a vessel. The balloon is then hydraulically inflated to stretch and compact the occlusive material and thus reopen the vessel. Balloon angioplasty can be effective but has the drawback that the thrombus is merely compacted and not actually removed. The remaining thrombus can quickly promote the reocclusion of the involved vessel. Balloon angioplasty also has the attendant risks of internal rupture or dissection of the vessel, vasospasm, and stimulation of internal hyperplasia which results in restenosis of the vessel. Furthermore, balloon angioplasty cannot be used in vessels too small for passage of the balloon catheter.
There exist other methods for reopening occluded vessels. Most of which involve mechanical devices that bore and drill through the thrombus. Because of their large caliber, inflexibility, and potential for severe damages to vessel walls, their usefulness is limited. Recently there have been a number devices have been developed that utilize ultrasonic energy to break up thrombus and other occluding materials. The general design involves an extracorporeal transducer coupled to a solid metal wire which is threaded through the vessel and placed in contact with the occlusion. Ultrasonic energy generated by the transducer is conducted along the solid metal wire to its up. The tip, vibrating at around 20-30 kHz, strikes the occlusive material and causes it to break up largely through mechanical interaction. Because ultrasonic energy must be efficiently transmit along considerable distances, the wires (usually of titanium or aluminum alloy) are relatively stiff and have relatively large diameters. Therefore, these ultrasonic devices cannot be effectively steered into tortuous or small vessels. The stiffness of the solid transmission wires also increases the potential for vessel wall injuries such as dissection and rupture. The other problem facing this type of design is that the tip of the wire vibrates mostly in a longitudinal fashion so that the ultrasonic energy cannot be effectively focused or directed. Examples of this type of design can be found in U.S. Pat. No. 5,269,297 to Weng, U.S. Pat. No. 5,326,342 to Pflueger, and U.S. Pat. No. 5,397,293 to Alliger.
In other attempts to utilize ultrasonic energy to reopen occluded vessels, a number of in vitro experiments have examined the effect of external ultrasonic irradiation on thrombolysis by pharmacologic agents. Such study is described in Lauer, CG et al:, Effect of ultrasound on tissue-type plasminogen activator-induced thrombolysis. Circulation. 86(4): 1257-1264, 1992. The results of these studies indicate that the combination of ultrasound and pharmacologic agents greatly accelerates the process of thrombolysis. Unlike the ultrasonic transmission wire described above, there is no direct mechanical disruption of thrombus in this method because there is no physical contact between the ultrasound delivery device and the thrombus. Ultrasonic energy impinging on the thrombus is transmitted through a liquid medium from a transducer. The exact mechanism of thrombolysis enhancement by ultrasonic irradiation is still under investigation, but it is thought that ultrasound facilitates the penetration of pharmacologic agents into the thrombus. Because the lytic action of these agents is surface area dependent, greater permeation means faster thrombolysis.
There are catheters with ultrasonic transducer at their tip such as the catheter disclosed in U.S. Pat. No. 4,917,097 to Proudian. These catheters are used for ultrasonic imaging of vessels, and because these catheters are designed for imaging purposes, ultrasonic generating piezoelectric elements are disposed to direct most of the generated high frequency ultrasonic energy toward the vessel walls. Further, because the piezoelectric elements of these catheters must also function as receivers of ultrasonic signals bounced back from the vessel walls, the devices are unable to deliver relatively high intensity ultrasonic energy. The amplitude of the ultrasound is reduced because the piezoelectric elements must stop emitting ultrasonic energy during the time they act as signal receivers.
Experimental research has shown that significant enhancement of thrombolysis occurs using ultrasonic intensity well above that used for imaging purposes (Olsson SB et al., Enhancement of thrombolysis by ultrasound, Ultrasound in Medicine and Biology, 20(4):375-382, 1994). Therefore, the low amplitude ultrasonic transducers of these imaging catheters cannot, nor are they intended to, enhance thrombolysis. The energy conversion efficiencies of ultrasound imaging transducers are generally not high enough to be used at the levels needed for thrombolysis, and such imaging transducers could be destroyed by the generated heat at the energy levels needed for thrombolysis.
Furthermore, many of these catheters have integrated circuitry in their tips and contain transmission cables comprising a large number conductors, all of which result in inflexible catheters with relatively large diameter. In fact, to obtain adequate imaging resolution as many as 32-64 sensors and their corresponding sensing wires must be included in the catheter. Even when the signal is multiplexed by tip circuitry, the minimum number of catheter wires still remains at eight, which together with the bulk of the electronic circuitry virtually excludes the use of such catheters in small or tortuous vessels.
While it has been demonstrated that ultrasonic irradiation enhances pharmacologic thrombolysis, and while ultrasound energy can be transmitted from the tip of a catheter for imaging purposes, no effective means of delivering ultrasound energy to a thrombotic vessel for pharmacologic thrombolysis is presently available. For this purpose one needs a flexible, minimal profile ultrasound delivery device that is capable of navigating small, tortuous channels in order reach the thrombotic site. Further, this device must be capable of delivering ultrasonic energy in a directed fashion at a relatively high amplitude while, at the same time, delivering thrombolytic agents. Such a device would enhance the procedure of pharmacologic thrombolysis by reducing the treatment time and/or the amount of pharmacologic agents administered. These reductions would minimize the potential for severe complications.